How best to structure a laboratory network with new technologies

Transcription

1 How best to structure a laboratory network with new technologies Cristina Gutierrez, MD, PhD Uniting to scale up TB care in Central Asia 14 and 15 April 2011 Tashkent, Uzbekistan

2 New laboratory diagnostics for TB and MRD-TB WHO endorsement Technology Detects Turnaround time Sensitivity Gain Before 2007 ZN microscopy TB 2-3 days Baseline Before 2007 Solid Culture & DST TB & MDR-TB days Baseline 2007 Liquid Culture & DST TB & MDR-TB days +10% compared to LJ 2008 Line Probe Assay (1st line, Rif-INH) TB & MDR-TB 2-4 days At this time for smear + only 2009 LED-based FM TB 1-2 days +10% compared to ZN Conditional 2009 In house DST (MODS, CRI, NRA) TB & MDR-TB days 1 st line only 2010 GeneXpert TB & Rif R-TB 2 hours +40% compared to ZN Importance for early diagnosis & care smear-negative TB rapid MDR detection

3 Introducing high tech in low tech settings Major advantages in workflow 3 GeneXpert Automated Sample Prep, Amplification and Detection <120 minutes A technology platform: TB & Rif Resistance Potential for HIV viral load Potential for HPV STD fully automated with 1-step external sample prep. time-to-result 1,5 h (walk away test) throughput: up to 16 tests/module/day no bio-safety cabinet closed system (lower contamination risk) Performance specific for MTB sensitivity close to culture detection of rif-resistance via rpob gene

4 The slow road to TB diagnosis

5 Importance of early diagnosis: Sensitivity (cfu/ml) of pulmonary TB tests iled fluorescent microscope 10,000/ml Capilia speciation dipstick (of culture) 1,000,000/ml LAMP-TB /ml Line-probe 10,000/ml MGIT /ml Xpert MTB /ml Log cfu/ml

6 Integration of new tools in the tiered health system Surveillance Reference methods Network supervision Reference Labs 5 % Resolution testing (screening-test negative drug resistance) Regional Labs SC / DST 30d / 60d 10 % District Screening Passive case finding Detect and treat SubDistrict ZN 2-3d 25 % Microscopy Clinical Screening Primary care Community 60 % Fraction of patients seen

7 Integration of new tools in the tiered health system Surveillance Reference methods Network supervision Reference Labs LC / DST 15d/ 30d 5 % Resolution testing (screening-test negative drug resistance) Regional Labs LPA Rif / INH 2d Early Infant DX HIV 10 % District Screening Passive case finding Detect and treat SubDistrict Integrated NAAT +40% /2h Sputum neg./hiv pos. HIV Viral Load 2012 HPV STD % Microscopy LED FM +10% Clinical Screening Primary care Community 60 % Fraction of patients seen

8 Integration of new tools in the tiered health system Surveillance Reference methods Network supervision Reference Labs LC / DST 15d/ 30d 5 % Resolution testing (screening-test negative drug resistance) Regional Labs LPA Rif / INH 2d Early Infant DX HIV 10 % District Screening Passive case finding Detect and treat SubDistrict Integrated NAAT +40% /2h Sputum neg./hiv pos. HIV Viral Load 2012 HPV STD % Microscopy LED FM +10% Manual NAAT+25% EID HIV 2011 Malaria HAT Clinical Screening Primary care Community RDT Gen1 / Gen 2 60 % Fraction of patients seen

9 Decentralization of molecular diagnostics 1st generation MDR 2nd generation automated MDR 1st generation manual detection 2nd generation manual detection LPA Xpert LAMP POC test

10 Expanding the access to new diagnostics ( ) Integrating new tools in national TB control programs Improving MDR-TB control Improving market dynamics Rapid MTB speciation Liquid culture and DST Line Probe Assay Assessment visit Memorandum of understanding Infrastructure and equipment Training 27 countries 101 laboratories (42 in India) Technical validation Reporting 30% MDR-TB cases Mentor ship Impact evaluation

11 The rational for introducing new TB tests in a network Disease burden, size of the country, level of decentralization Eligible patient to be tested and diagnostic algorithm Smear + and/ or Any case or only any drug resistant suspect or only MDR suspects Low and high HIV settings Low and high MDR settings Specimen/patient referral Linkage to treatment Costs and donors support Technical realities and implementation challenges

12 Challenges of implementing new diagnostics A functional laboratory requires more than commodities Logistics and supplies Human Resources (Guidelines Technology transfer) Infrastructure Quality Assurance Linked referral systems and reporting Essential instruments, reagents, supplies Additional components to ensure quality diagnostic services

13 Challenges of implementing new diagnostics are tool-dependent Equipment and supplies, maintenance iled microscopy GeneXpert LPA Liquid culture and DST

14 Challenges of implementing new diagnostics are tool-dependent iled microscopy GeneXpert LPA Liquid culture and DST Laboratory infrastructure BSL1 BSL1 BSL2 and molecular rooms BSL3

15 Challenges of implementing new diagnostics are tool-dependent iled microscopy GeneXpert LPA Liquid culture and DST Human resources, training

16 Challenges of implementing new diagnostics are tool-dependent Supplies procurement and storage iled microscopy GeneXpert LPA Liquid culture and DST Waste management Laboratory Information Management System Communication of results

17 Challenges of implementing new diagnostics are tool-dependent Quality management system, with EQA, proficiency testing, IQC iled microscopy GeneXpert LPA Liquid culture and DST To maintain good performance and to assure high quality results

18 Internal Quality Controls, NTRL Lesotho Tuberculosis HIV-EID Liquid culture (MGIT) Drug susceptibility testing Smear microscopy Line Probe assay Amplicor HIV 1- DNA Media batch testing with H37Rv MRC cultures as internal standards- H37Rv and one mono rif (mainly) Batch testing of stains with known positive and negative slides- Centralized supply Mfg. run controls (CC, AC, TUB) Mfg. run controls (one high positive and one negative DBS) Monthly/ annual five performance indicators- Contamination rate; Corr-Smear & Culture Positive; NTM, rate, TAT etc., Temperature logs, equipment maintenance sheets for all tests IQC slides-one 1+ positive and one negative, every day before patients samples checking NRL Onsite EQA activities for all microscopy centers Water used in DNA extraction step and master-mix step controls (negative) Monitoring of statistics of test results and trends, monthly (to check what kind of samples are processed and what is TAT) CDC/GAP internal controls- (one high positive and one negative DBS) For all HIV-1 DNA positive, test is repeated, before providing results

19 External Proficiency Testing at NTRL Lesotho Tuberculosis Solid/Liquid culture (MGIT) & AFB smears Line Probe assay HIV-EID Amplicor HIV 1- DNA NHLS, South Africa (SA) MRC, Pretoria, SA MRC, Pretoria, SA GAP/CDC, Atlanta 3 blinded cultures isolates 1 lyophilized sample for culture, id and DST and 10 blinded smears (Quarterly) 10 culture isolates for DST (Annual) 10 culture isolates same as used in DST (Annual) 10 Dried Blood spot specimens sent by GAP (quarterly) 100% concordance with smear and culture results (2 nd quarter 2010) Achieved 95% concordance with rifampicin and 100% for isoniazid (2009) Achieved 95% concordance for rifampicin and 100% for isoniazid (2009) Achieved 100% concordance (1 st and 2 nd PT rounds, 2010)

20 Coordination with local stakeholders Internal and external quality assurance Technology transfer and training specimen referral mechanisms long-term, on-site mentoring Monitoring, evaluation and impact assessment National TB Programs implementing new technologies laboratory manageme nt SOPs Procurement Policy reform and adoption Biosafety standards Supply chain management

21 Thank you!